Beshbishy Amany Magdy, Batiha Gaber El-Saber, Alkazmi Luay, Nadwa Eman, Rashwan Eman, Abdeen Ahmed, Yokoyama Naoaki, Igarashi Ikuo
National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Nishi 2-13, Inada-cho 080-8555, Obihiro, Hokkaido, Japan.
Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour 22511, Al Beheira, Egypt.
Pathogens. 2020 Feb 17;9(2):127. doi: 10.3390/pathogens9020127.
Atranorin (ATR), is a compound with multidirectional biological activity under different in vitro and in vivo conditions and it is effective as an antibacterial, antiviral, antiprotozoal and anti-inflammatory agent. In the current study, the in vitro as well as in vivo chemotherapeutic effect of ATR as well as its combined efficacy with the existing antibabesial drugs (diminazene aceturate (DA), atovaquone (AV) and clofazimine (CF)) were investigated on six species of piroplasm parasites. ATR suppressed and multiplication in vitro with IC values of 98.4 ± 4.2, 64.5 ± 3.9, 45.2 ± 5.9, 46.6 ± 2.5, and 71.3 ± 2.7 µM, respectively. The CCK test was used to examine ATR's cytotoxicity and adverse effects on different animal and human cell lines, the main hosts of piroplasm parasites and it showed that ATR affected human foreskin fibroblasts (HFF), mouse embryonic fibroblast (NIH/3T3) and Madin-Darby Bovine Kidney (MDBK) cell viability in a dose-related effect with a moderate selective index. The combined efficacy of ATR with DA, CF, and AV exhibited a synergistic and additive efficacy toward all tested species. In the in vivo experiment, ATR prohibited multiplication in mice by 68.17%. The ATR-DA and ATR-AV combination chemotherapies were more potent than ATR monotherapy. These results indicate the prospects of ATR as a drug candidate for piroplasmosis treatment.
黑茶渍素(ATR)是一种在不同体外和体内条件下具有多向生物活性的化合物,作为抗菌、抗病毒、抗原虫和抗炎剂具有有效性。在本研究中,研究了ATR对六种梨形虫寄生虫的体外和体内化疗效果,以及它与现有抗巴贝斯虫药物(乙酰氨基苯脒(DA)、阿托伐醌(AV)和氯法齐明(CF))联合使用的疗效。ATR在体外抑制了[具体寄生虫名称]的增殖,其IC值分别为98.4±4.2、64.5±3.9、45.2±5.9、46.6±2.5和71.3±2.7μM。使用CCK试验检测ATR对不同动物和人类细胞系(梨形虫寄生虫的主要宿主)的细胞毒性和不良反应,结果表明ATR对人包皮成纤维细胞(HFF)、小鼠胚胎成纤维细胞(NIH/3T3)和马-达二氏牛肾细胞(MDBK)的细胞活力有剂量相关影响,选择性指数适中。ATR与DA、CF和AV联合使用对所有测试物种均表现出协同和相加疗效。在体内实验中,ATR使小鼠体内[具体寄生虫名称]的增殖减少了68.17%。ATR-DA和ATR-AV联合化疗比ATR单一疗法更有效。这些结果表明ATR作为梨形虫病治疗候选药物的前景。 (注:原文中部分具体寄生虫名称未明确写出,翻译时用[具体寄生虫名称]表示)